The long-range objectives of the proposed research are to contribute to the complete understanding of the pathogenesis and immunology of cholera. Results obtained by study of the cholera exo-enterotoxin (choleragen) and its interaction with the host may also be applicable to other enterotoxic enteropathies which depend on toxins related to the cholera enterotoxin immunologically and by mode of action in activating adenylate cyclase. The toxin unique region, A, and choleragenoid (the enterotoxoid equivalent to the B region) will be analyzed further to determine their interaction and roles in the causation and immunology of cholera. Efforts will be made to develop mutants and genetic hybrids which can colonize the gut and may elicit simultaneously both antibacterial and antitoxic immune mechanisms at the important local level. Other aspects of the pathogenesis of cholera such as the ability of the vibrios to colonize the gut will also come under investigation.